cSurvival: a web resource for biomarker interactions in cancer outcomes and in cell lines.

Survival analysis is a technique for identifying prognostic biomarkers and genetic vulnerabilities in cancer studies. Large-scale consortium-based projects have profiled >11 000 adult and >4000 pediatric tumor cases with clinical outcomes and multiomics approaches. This provides a resource for investigating molecular-level cancer etiologies using clinical correlations. Although cancers often arise from multiple genetic vulnerabilities and have deregulated gene sets (GSs), existing survival analysis protocols can report only on individual genes. Additionally, there is no systematic method to connect clinical outcomes with experimental (cell line) data. To address these gaps, we developed cSurvival (https://tau.cmmt.ubc.ca/cSurvival). cSurvival provides a user-adjustable analytical pipeline with a curated, integrated database and offers three main advances: (i) joint analysis with two genomic predictors to identify interacting biomarkers, including new algorithms to identify optimal cutoffs for two continuous predictors; (ii) survival analysis not only at the gene, but also the GS level; and (iii) integration of clinical and experimental cell line studies to generate synergistic biological insights. To demonstrate these advances, we report three case studies. We confirmed findings of autophagy-dependent survival in colorectal cancers and of synergistic negative effects between high expression of SLC7A11 and SLC2A1 on outcomes in several cancers. We further used cSurvival to identify high expression of the Nrf2-antioxidant response element pathway as a main indicator for lung cancer prognosis and for cellular resistance to oxidative stress-inducing drugs. Altogether, these analyses demonstrate cSurvival's ability to support biomarker prognosis and interaction analysis via gene- and GS-level approaches and to integrate clinical and experimental biomedical studies.

Ferroelectric domain engineering with femtosecond pulses of different wavelengths.

Direct femtosecond laser writing of ferroelectric domain structures has been an indispensable technique for engineering the second-order optical nonlinearity of materials in three dimensions. It utilizes localized thermoelectric field motivated by nonlinear absorption at the position of laser focus to manipulate domains. However, the impact of laser wavelengths, which is pivotal in nonlinear absorption, on the inverted domains is still sketchy. Herein, the light-induced ferroelectric domain inversion is experimentally studied. It is shown that the domain inversions can be achieved over a broad spectral range, but the optical threshold for domain inversion varies dramatically with the laser wavelength, which can be explained by considering the physical mechanism of femtosecond laser poling and nonlinear absorption properties of the crystal. Meanwhile, the effects of other laser processing parameters are also experimentally investigated. Our findings are useful to guide the fabrication of high-performance optical and electronic devices based on ferroelectric domains.

eVITTA: a web-based visualization and inference toolbox for transcriptome analysis.

Transcriptome profiling is essential for gene regulation studies in development and disease. Current web-based tools enable functional characterization of transcriptome data, but most are restricted to applying gene-list-based methods to single datasets, inefficient in leveraging up-to-date and species-specific information, and limited in their visualization options. Additionally, there is no systematic way to explore data stored in the largest transcriptome repository, NCBI GEO. To fill these gaps, we have developed eVITTA (easy Visualization and Inference Toolbox for Transcriptome Analysis; https://tau.cmmt.ubc.ca/eVITTA/). eVITTA provides modules for analysis and exploration of studies published in NCBI GEO (easyGEO), detailed molecular- and systems-level functional profiling (easyGSEA), and customizable comparisons among experimental groups (easyVizR). We tested eVITTA on transcriptomes of SARS-CoV-2 infected human nasopharyngeal swab samples, and identified a downregulation of olfactory signal transducers, in line with the clinical presentation of anosmia in COVID-19 patients. We also analyzed transcriptomes of Caenorhabditis elegans worms with disrupted S-adenosylmethionine metabolism, confirming activation of innate immune responses and feedback induction of one-carbon cycle genes. Collectively, eVITTA streamlines complex computational workflows into an accessible interface, thus filling the gap of an end-to-end platform capable of capturing both broad and granular changes in human and model organism transcriptomes.

Serum VCAM-1 and ICAM-1 measurement assists for MACE risk estimation in ST-segment elevation myocardial infarction patients.

BACKGROUND: Vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) modulate atherosclerosis by promoting leukocyte infiltration, neutrophil recruitment, endothelial cell proliferation, etc., which may directly or indirectly facilitate the occurrence of major adverse cardiac events (MACE). This study intended to investigate the value of VCAM-1 and ICAM-1 for predicting MACE in ST-segment elevation myocardial infarction (STEMI) patients. METHODS: Totally, 373 STEMI patients receiving the percutaneous coronary intervention and 50 health controls (HCs) were included. Serum VCAM-1 and ICAM-1 were detected by ELISA. Meanwhile, MACE was recorded during a median follow-up of 18 (range: 1-46) months in STEMI patients. RESULTS: Vascular cell adhesion molecule-1 and ICAM-1 were raised in STEMI patients compared with HCs (both p < 0.001). VCAM-1 (p = 0.002) and ICAM-1 (p = 0.012) high were linked with raised accumulating MACE rate in STEMI patients. Notably, VCAM-1 high (hazard ratio [HR] = 2.339, p = 0.031), age ≥ 65 years (HR = 2.019, p = 0.039), history of diabetes mellitus (DM) (HR = 2.395, p = 0.011), C-reactive protein (CRP) ≥ 5 mg/L (HR = 2.550, p = 0.012), multivessel disease (HR = 2.561, p = 0.007) independently predicted MACE risk in STEMI patients. Furthermore, a nomogram-based prediction model combining these factors was established, exhibiting an acceptable value for estimating 1, 2, and 3-year MACE risk, with AUC of 0.764, 0.716, and 0.778, respectively, in STEMI patients. CONCLUSION: This study confirms the value of VCAM-1 and ICAM-1 measurement in predicting MACE risk in STEMI patients. Moreover, VCAM-1 plus other traditional prognostic factors (such as age, history of DM, CRP, and multivessel disease) cloud further improve the predictive accuracy of MACE risk in STEMI patients.

Generation of watt-level supercontinuum covering 2-6.5 µm in an all-fiber structured infrared nonlinear transmission system.

We demonstrate a watt-level mid-infrared supercontinuum source, with the spectrum covering the infrared region from 2 to 6.5 µm, in an all-fiber structured laser transmission system. To further improve the SC spectral bandwidth, power and system compactness in the follow-up As2S3 fiber, we theoretically and experimentally explored some knotty problems that would potentially result in the As2S3 fiber end-facet failure and low SC output power during the high-power butt-coupling process and proposed an optimal coupling distance on the premise of the safety of As2S3 fiber end face. In addition, we also built a multi-pulse pumping model for the first time to more precisely estimate the SC spectral evolution in As2S3 fiber. This work will give an important reference to someone who is working on the all-fiber structured, high-power mid- and far-infrared supercontinuum source.

Schottky Barrier Induced Coupled Interface of Electron-Rich N-Doped Carbon and Electron-Deficient Cu: In-Built Lewis Acid-Base Pairs for Highly Efficient CO2 Fixation.

Highly efficient fixation of CO2 for the synthesis of useful organic carbonates has drawn much attention. The design of sustainable Lewis acid-base pairs, which has mainly relied on expensive organic ligands, is the key challenge in the activation of the substrate and CO2 molecule. Here, we report the application of Mott-Schottky type nanohybrids composed of electron-deficient Cu and electron-rich N-doped carbon for CO2 fixation. A ligand-free and additive-free method was used to boost the basicity of the carbon supports and the acidity of Cu by increasing the Schottky barrier at their boundary, mimicking the beneficial function of organic ligands acting as the Lewis acid and base in metal-organic frameworks (MOFs) or polymers and simultaneously avoiding the possible deactivation associated with the necessary stability of a heterogeneous catalyst. The optimal Cu/NC-0.5 catalyst exhibited a remarkably high turnover frequency (TOF) value of 615 h-1 at 80 °C, which is 10 times higher than that of the state-of-the-art metal-based heterogeneous catalysts in the literature.

Vitamin D Deficiency Harms Patients with Coronary Heart Disease by Enhancing Inflammation.

BACKGROUND Vitamin D (VD) deficiency and local inflammation of plaque are potential new risk factors and prevention goals for coronary heart disease (CHD). MATERIAL AND METHODS This study included 135 CHD patients and 45 chest tightness or chest pain patients (control group). Basic clinical data and serum 25-OH-VD, TNF-α, IL-6, IL-8, and IL-1ß of the 2 groups were compared by SPSS 25.0. A CHD rat model was used to explore the potential molecular mechanisms. RESULTS The serum 25-OH-VD level in the control group was significantly higher compared to the CHD group, and decreased with the worsening of the CHD condition. Logistic regression found that serum 25-OH-VD was a protective factor in the occurrence of CHD. In CHD patients, the level of serum 25-OH-VD had a negative correlation with serum TNF-α (r=-0.651, P<0.001), IL-6 (r=-0.457, P<0.001), IL-8 (r=-0.755, P<0.001), and IL-1ß (r=-0.628, P<0.001). In animal experiments, VD deficiency enhanced the level of serum TC, TG, and LDL-C. VD deficiency could increase the inflammatory response by upregulating the expression of p65 protein and reducing SIRT1 protein expression in heart tissue, thereby inducing or aggravating the state of CHD. CONCLUSIONS Serum 25-OH-VD was a protective factor in the occurrence of CHD, and VD deficiency could induce or aggravate the state of CHD by enhancing inflammation through the NF-κB pathway.

Study of coronary artery perforation during percutaneous coronary intervention in the Cangzhou Chinese population.

OBJECTIVE: Coronary artery perforation (CAP) is a rare, serious complication of percutaneous coronary intervention (PCI). Many studies have addressed the incidence, risk factors, and management of CAP in different countries except China. The aim of this study is to determine the risk factors and types of treatment for coronary perforation occurring in patients undergoing PCI and living in the Cangzhou Chinese population. METHODS AND RESULTS: A retrospective cohort of 12,113 patients who underwent PCI was used: 64 patients with CAP and 192 case-control patients were evaluated. Clinical data and findings from coronary arteriography and PCI were analysed. Logistic regression was used to evaluate candidate risk factors for CAP. The treatments were also evaluated. The incidence of CAP in patients undergoing PCI was 0.53%, and the mortality was 7.8% (5/64). Risk factors included female gender, hypertension, non-ST-elevation acute coronary syndrome (NSTE-ACS), right coronary artery (RCA) lesion, calcified lesion, and chronic total occlusion (CTO) (all P < 0.05, all OR > 1). CTO had the highest risk (OR = 5.077, P < 0.001). Patients with class I CAP underwent conservative treatment. Patients with class II CAP underwent conservative treatment or low-pressure balloon dilatation (61.1% and 22.2%, respectively). Patients with class III CAP underwent low-pressure balloon dilatation, coated-stent implantation, and emergency surgery (40.9%, 27.3%, and 22.7%, respectively). CONCLUSIONS: CAP risk factors in Cangzhou Chinese patients undergoing PCI included CTO, NSTE-ACS, hypertension, calcified and RCA lesions, and female gender. Different treatment methods should be used according to the different classes of CAP.

Radial glia cells are candidate stem cells of ependymoma.

Tumors of the same histologic type often comprise clinically and molecularly distinct subgroups; however, the etiology of these subgroups is unknown. Here, we report that histologically identical, but genetically distinct, ependymomas exhibit patterns of gene expression that recapitulate those of radial glia cells in the corresponding region of the central nervous system. Cancer stem cells isolated from ependymomas displayed a radial glia phenotype and formed tumors when orthotopically transplanted in mice. These findings identify restricted populations of radial glia cells as candidate stem cells of the different subgroups of ependymoma, and they support a general hypothesis that subgroups of the same histologic tumor type are generated by different populations of progenitor cells in the tissues of origin.

Enhancing interface stability and ionic conductivity in the designed Na3SbP0.4xS4-xOx sulfide solid electrolyte through bridging oxygen.

The all-solid-state sodium battery has emerged as a promising candidate for energy storage. However, the limited electrochemical stability of the solid electrolyte, particularly in the presence of Na metal at the anode, along with low ionic conductivity, hinders its widespread application. In this work, the design of P and O elements in Na3SbS4 solid electrolyte was investigated through a series of structural tests and characterizations. The electrochemical stability was remarkably improved in the Na/Na3SbP0.16S3.6O0.4/Na battery, exhibiting a stability of 260 h under a current of 0.1 mA cm-2. Additionally, the room temperature conductivity of Na3SbP0.16S3.6O0.4 was enhanced to 3.82 mS cm-1, maintaining a value comparable to commercial standards. The proposed design strategy provides an approach for developing sodium ion solid-state batteries with high energy density and long lifespan. The stability of the solid electrolyte interface at the Na | solid electrolyte interface proves critical for the successful assembly of all-solid-state sodium ion batteries.

Designed anion and cation co-doped Na3Sb(WM)xS4 (M = Cl, Br, I) sulfide electrolytes with an improved conductivity and stable interfacial qualities.

The fabrication of all electrolytes from noncombustible ceramic materials offers a superior option for providing safer and higher-capacity batteries to fulfill future energy needs. To achieve a competitive performance with combustible liquid electrolytes used in commercial Li-ion batteries, the creation of ceramic material compositions with a high electrical conductivity is necessary. Here, we report that co-doping with W and halogens results in a superconductivity of 13.78 mS cm-1 in a cubic-phase Na3SbS4 glass ceramic electrolyte. After undergoing high-temperature heat treatments, the W ions in the electrolyte can facilitate the replacement of S atoms with halogens, introducing many Na vacancies. The samples also had a high degree of cycling stability. An excellent glass ceramic electrolyte for Na ion batteries will be constructed for Na3SbW0.25Cl0.25S4.

Effect of expansion media containing fibroblast growth factor-2 and dexamethasone on the chondrogenic potential of human adipose-derived stromal cells.

hASCs [human ASCs (adipose derived stromal cells)] proliferate more rapidly in the presence of basic FGF-2 (fibroblast growth factor-2) and Dex (dexamethasone). We have examined the effects of expanding hASCs in media containing these two factors on their chondrogenic differentiation potential. Results show that the addition of FGF-2 and Dex to the expansion medium does not remarkably alter the chondrogenic potential of the cells induced by BMP-6 (bone morphogenetic protein-6), based on chondrogenic gene expression, sGAG (sulfated glycosaminoglycan) accumulation and immunohistochemical observation. This is in direct contrast to previously reported promotion of the osteogenic and adipogenic potential of hASCs by these two factors. Therefore, an expansion medium containing FGF-2, with or without Dex, is appropriate for the fast expansion of hASCs without compromising chondrogenic potential.

Analysis of the Guiding Role of CYP2C19 Gene Combined With Platelet Function Detection in Antiplatelet Therapy in Patients With Complex Coronary Artery Disease After PCI.

OBJECTIVE: To explore the influence of CYP2C19 gene combined with platelet function test on clinical prognosis of patients with complex coronary artery disease receiving antiplatelet therapy after PCI. METHODS: A total of 200 patients undergoing PCI in our hospital due to complex coronary artery disease from February 2019 to February 2021 were selected and divided into the control group and the observation group according to whether CYP2C19 gene detection was performed. The control group was treated with dual antiplatelet therapy of classical aspirin combined with clopidogrel, and the observation group was treated with individual antiplatelet therapy. The patients in the two groups were followed up for 1 year after PCI, and their quality of life was assessed using the Seattle Angina Questionnaire (SAQ score). The occurrence of major adverse cardiovascular events (MACE) during the follow-up period was also recorded. RESULTS: The incidence of total MACE events in the observation group was slightly less than that in the control group, and the difference was statistically significant (P = 0.040). In particular, the observation group was superior to the control group in reducing the readmission rate of recurrent unstable angina pectoris, and the difference was statistically significant (P = 0.023). The location of coronary culprit lesions with recurrent ischemic events was commonly seen in non-interventional target lesions (interventional/non-interventional target sites: 12.9%: 77.1%). The SAQ score in the observation group was larger than that in the control group, and the difference was statistically significant (P = 0.012). There was no statistical difference in the incidence of major bleeding between the two groups (P = 0.352). CONCLUSION: Using CYP2C19 genotype combined with platelet function test to guide individualized antiplatelet therapy after complex coronary artery PCI is beneficial to reducing ischemic events in a short period (1 year), mainly due to reducing the risk of readmission for recurrent unstable angina pectoris, and improving the quality of daily life of patients without increasing the risk of massive hemorrhage, which can improve clinical prognosis.

Mild and selective hydrogenation of CO2 into formic acid over electron-rich MoC nanocatalysts.

The direct hydrogenation of CO2 using H2 gas is a one-stone-two-birds route to produce highly value-added hydrocarbon compounds and to lower the CO2 level in the atmosphere. However, the transformation of CO2 and H2 into hydrocarbons has always been a great challenge while ensuring both the activity and selectivity over abundant-element-based nanocatalysts. In this work, we designed a Schottky heterojunction composed of electron-rich MoC nanoparticles embedded inside an optimized nitrogen-doped carbon support (MoC@NC) as the first example of noble-metal-free heterogeneous catalysts to boost the activity of and specific selectivity for CO2 hydrogenation to formic acid (FA) in liquid phase under mild conditions (2 MPa pressure and 70 °C). The MoC@NC catalyst with a high turnover frequency (TOF) of 8.20 molFA molMoC-1 h-1 at 140 °C and an excellent reusability are more favorable for real applications.

Circulating miR-130 and its target PPAR-γ may be potential biomarkers in patients of coronary artery disease with type 2 diabetes mellitus.

BACKGROUND: Patients of coronary artery disease (CAD) with type 2 diabetes mellitus (DM2) show increased mortality risk than CAD patients without DM2, while few biomarkers can be used to discriminate them. METHODS: Fifty-nine patients of CAD with DM2 (DM2-CAD group), 79 patients of CAD without DM2 (CAD group), and 63 healthy control subjects were recruited. Circulating miR-130 (miR-130a and miR-130b) and PPAR-γ (peroxisome proliferator-activated receptor gamma) were measured and their Pearson correlation was analyzed. 3' UTR binding prediction and luciferase assay were used to determine the target relationship between miR-130 and PPAR-γ. Receiver operating characteristics (ROC) analysis was performed to test the discrimination ability of miR-130 between DM2-CAD and CAD groups. RESULTS: miR-130a and miR-130b showed decreased expression in DM2-CAD group when compared with the CAD group and health control. Both bioinformatics and luciferase assays showed that miR-130 could bind the 3' UTR of PPAR-γ. Furthermore, miR-130 negatively correlated with PPAR-γ in both CAD and DM2-CAD group in Pearson's coefficient analysis. Both miR-130a and miR-130b were able to discriminate DM2-CAD group from CAD group and control subjects. CONCLUSION: Circulating miR-130 may regulate the expression of PPAR-γ and can be used as a biomarker to discriminate DM2-CAD from CAD.

The effect of titanium surface roughening on protein absorption, cell attachment, and cell spreading.

PURPOSE: The purpose of this study was to compare properties of roughened and polished titanium with respect to their ability to attach to cells and bind to protein as well as their cell spreading behavior. MATERIALS AND METHODS: Three different titanium surface treatments were compared for their ability to support cell attachment and spreading: sandblasted and acid-etched, resorbable blast media, and machine-polished titanium. The surface of the materials was characterized for surface roughness, surface energy, and surface chemistry. Osteoblast-like MG-63 cells were tested for in vitro attachment and spreading in the presence of serum proteins. Cell attachment was assessed by direct counting, dye binding, and microculture titanium assays. Cell spreading was determined by measuring area/cell in phalloidin-AlexaFluor 488 stained cells. Absorption of bovine serum albumin was determined by assay. RESULTS: Scanning electron micrography and x-ray diffractometry confirmed increased surface roughness of the roughened materials. All 3 materials had similar albumin binding kinetics. Three different methods confirmed that roughened surfaces enhance early cell attachment to titanium in the presence of serum. Cells spread better on smoother machined surfaces than on the roughened surfaces. CONCLUSION: Roughened titanium surfaces exhibited better early cell attachment than smooth surfaces in the presence of serum. The cells attached to roughened titanium were less spread than those attached to machined titanium. Although albumin binding was not different for roughened surfaces, it is possible that roughened surfaces preferentially bound to serum adhesive proteins to promote early cell attachment.

Novel fabrication of nano-rod array structures on titanium and in vitro cell responses.

Nano-scale rod arrays of titania were fabricated on titanium surface by a glass phase topotaxy growth (GPT) method, which was featured by an interfacial reaction between sodium tetraborate coating and the preheated metallic titanium at elevated temperature. The samples were characterized by thin-film X-ray diffraction (XRD), scanning electron microscope (SEM), profilometer and contact angle measurement. Thin-film XRD analysis indicated that the nano-rod arrays were composed of pure rutile titania phase. SEM images showed that these rutile rods were 100-200 nm wide and 1-2 microm long. The nano-rod arrays had significantly higher average roughness (P < 0.05) and greater hydrophilicity (P < 0.05) compared to the control. Human embryonic palatal mesenchymal (HEPM) cells were grown to evaluate in vitro cell responses to the nano-rod array structures in terms of cell attachment and proliferation. An equivalent high attachment rate of 94% was observed after 4-h incubation, but a lower proliferation rate was observed on the nano-rod array after 12-day culture compared to the control (P < 0.05).

Palmatine attenuates isoproterenol-induced pathological hypertrophy via selectively inhibiting HDAC2 in rats.

This study aimed to exploit the potential therapeutic value of palmatine in treatment of cardiac hypertrophy and the underlying molecular mechanism. Rat hypertrophy model was established by intraperitoneal isoproterenol (ISO) injection. The hypertrophy was evaluated with cardiac hypertrophic parameters, hemodynamic parameters, lipid profile, and non-specific cardiac markers. The animals were intraperitoneally administrated with either palmatine or vehicle. The relative expressions of ANP, BNP, HDAC2, HDAC5, KLF4, and INPP5F transcripts were determined by real-time polymerase chain reaction (PCR). The relative protein levels of HDAC2, HDAC5, KLF4, and INPP5F were analyzed by immunoblotting. Palmatine treatment significantly attenuated ISO-induced hypertrophy in rats and elicited remarkable repressions in ANP, BNP, and HDAC2 transcriptions but not HDAC5. The downstream effector genes KLF4 and INPP5F were greatly restored in a dose-dependent manner in response to palmatine treatment. Our data demonstrated that palmatine possessed promising therapeutic potential against hypertrophy, which was mediated by modulation of HDAC2-KLF4/INPP5F pathway.

The solution-phase process of a g-C3N4/BiVO4 dyad to a large-area photoanode: interfacial synergy for highly efficient water oxidation.

The oxygen evolution reaction (OER) is the rate-limiting process for water splitting, and highly efficient large-area OER photoanodes have been considered as an essential part in photoelectrochemical water splitting reactors. The high hole-electron separation efficiency of photoanodes is highly required for real applications of photoanodes in sufficiently harvesting solar energy. Herein we show that the inactive g-C3N4 nanolayers can be self-assembled with BiVO4 into a highly coupled BV/CN dyad to significantly enhance the charge separation efficiency of BiVO4 photoelectrodes for the OER. The incident photon-to-current conversion efficiency (IPCE) of visible light (400 nm) provided by the scalable BV/CN-5 photoanode was estimated to be 50% at 1.23 V vs. RHE in 0.5 M Na2SO4 solution and significantly increased to 97% at a bias voltage of 1.6 V vs. RHE.